DESCRIPTION: The cause of selective dopamine neuron loss associated with Parkinson's disease (PD) is unknown. There has been growing interest in understanding the role of endogenous antioxidants in controlling oxidative stress, as well as being potential therapeutic agents in slowing the progression of PD. The long-term objective of this application is to generate experimental evidence on the role of uric acid as an endogenous antioxidant. This proposal describes experiments designed to determine if uric acid functions as a neuroprotector by investigating whether increasing or decreasing endogenous uric acid levels has an effect on the destruction of dopamine cells. This will be achieved by treating guinea pigs with purine enzyme inhibitors concomitantly with the dopamine neurotoxin MPTP. The specific aim of this proposal is to determine if changes in uric acid levels in the nigrostriatal system can influence the degree of dopamine cell death in the guinea pigs following MPTP treatment.